KR20160022751A

KR20160022751A - Microfluidic inspection apparatus and operating method therefor

Info

Publication number: KR20160022751A
Application number: KR1020140180159A
Authority: KR
Inventors: 치아-후이 린; 보 유; 이-펑 양
Original assignee: 샤오싱 푸쉬캉 바이오테크놀로지 컴퍼니 리미티드
Priority date: 2014-08-20
Filing date: 2014-12-15
Publication date: 2016-03-02
Also published as: US9737890B2; TW201608242A; CN105353159B; CN105353159A; US20160051986A1; TWI550274B

Abstract

The present invention relates to a microfluidic inspection apparatus having an operating module and a microfluidic platform. The operating module of the microfluidic inspection apparatus comprises a rotating unit and a vibrating unit which can be operated to move the microfluidic platform. The microfluidic platform comprises multiple microfluidic structures and thus can inspect and analyze a sample. Also, the present invention provides an operating method of the microfluidic inspection apparatus, which comprises a step of conveying the sample to multiple regions of the microfluidic structures using operating power provided by the rotating unit or the vibrating unit. The microfluidic inspection apparatus has an inexpensive price and can be easily manufactured while having remarkable stability. Further, the microfluidic inspection apparatus can complete inspection and analysis of a little amount of a sample in a short period of time.

Description

TECHNICAL FIELD [0001] The present invention relates to a microfluidic device and a method of operating the microfluidic device. [0002] MICROFLUIDIC INSPECTION APPARATUS AND OPERATING METHOD THEREFOR [0003]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a microfluidic examination apparatus and a method of operating the apparatus, and more particularly, to an apparatus and a method for transferring a fluid using a rotation system.

For conventional testing and testing, sample preprocessing and sample weighting are very complex and time-consuming tasks, and large test equipment and expert articles are required to obtain samples suitable for inspection and testing. However, it is very difficult to establish analytical laboratories because of the expensive expert training and investment in testing instruments. A large research center or hospital can establish an analytical department, but the smallest clinic on the front line lacks the capacity to have its own laboratory. These mini-clinics typically outsource sample inspection and analysis tasks to specialized laboratories. In this case, however, not only does it take a long time to transport the sample, but it can also result in deterioration of the sample or poor inspection and analysis quality.

Recently, lab-on-a-chip products have been successfully developed to overcome these disadvantages. Typical advantages of a lab-on-a-chip product include low fluid volume consumption, low manufacturing cost, rapid analysis, and convenient portability. Lab-on-a-chip technology has become an important part of global health. In particular, it has facilitated the development of point-of-care testing (POCT) equipment, which allows rapid inspection of casualties at the scene of the accident and medical services in the field, even in rural or remote areas. As with existing technologies, sample preprocessing steps and sample-based weighing are important factors in improving the inspection accuracy of devices based on lab-on-a-chip.

Portable inspection instruments, which are currently commercially available, often lack sample preprocessing capabilities and are therefore inconsistent as a result of inspection of devices based on lab-on-a-chip. For example, a cholesterol meter and a blood glucose meter which are frequently encountered in daily life are small and portable, which is very convenient to use. However, these lab-on-a-chip-based devices use less unprocessed samples and use capillary absorbers to transfer samples to laboratories in the instrument, resulting in less accurate tests. The accuracy of these devices is not suitable for use in healthcare facilities that assess patients' overall health status based on accurate data.

Centrifugation is a commonly used method for sample pretreatment. Centrifugation cleans the required sample quickly and at low cost. Centrifugation separates the sample using centrifugal force and material density, ultimately improving the accuracy of the test. For example, EPA staff can use centrifugation to isolate suspended solids in water samples and then perform colorimetric analysis with supernatant. As another example, a laboratory technician can use centrifugation to separate solid precipitate from a sample of urine and then analyze the precipitate with a microscope to inspect the urine of crystallization.

Sample weighing is another important procedure for lab-on-a-chip technology. In the field of bioanalysis, samples must generally be volumetrically reduced to reduce errors or variability in the process. For example, in a control experiment, the results of reactions of positive control groups and negative control groups are often used to set reference values or standard curves, and the reaction results of unknown samples can be compared with reference values. A common pre-requisite for control experiments is that the control sample and the unknown sample must be reacted in the same volume or the same conditions, such as the same temperature.

However, devices based on lab-on-a-chip, now commercially available, are lacking in high-quality volumetric capacity. Typical volumetric metering methods can be divided into manual and machine metering methods. The manual weighing method has a disproportionate distribution of the inspection sample and the sample due to an artificial mistake, which significantly affects the inspection result. For example, the concentration of triglycerides in blood of healthy adults should be less than 200 mg / mL. Assuming that a 6-μL plasma is injected into the test chamber of the device and that a mistake that occurred during the test procedure caused 8 μL of plasma to be injected, this mistake makes a marked difference in test results. Subjects with original triglyceride levels of 180 mg / mL in the plasma are diagnosed as belonging to the high risk group of cardiovascular disease because the test result is 240 mg / mL. The mechanical metering system generally distributes the liquid using a capillary tube or a wax plug. However, there is a problem that the capillary absorption tube and the wax plug are very unstable and difficult to manufacture.

Therefore, there is a need for a device based on a lab-on-a-chip that is easy to manufacture, very stable, and inexpensive.

In the embodiments of the present invention described herein, a microfluidic examination apparatus and a method of operating the apparatus are introduced. In particular, the microfluidic examination apparatus described in at least one of the embodiments is inexpensive, easy to manufacture, and excellent in stability. And you can finish the inspection and analysis in a short time using a small amount of sample. The microfluidic device quickly completes the sample preprocessing and sample metering procedures using a rotation and vibration scheme.

At least one of the embodiments of the present invention is a microfluidic inspection apparatus comprising one drive module and one microfluidic platform. The drive module has one rotating unit and one vibrating unit, which drives and controls the microfluidic platform. The microfluidic platform is mounted on the drive module. And the microfluidic platform contains at least one rotation center and at least one microfluidic structure that performs sample preprocessing and sample metering. Microfluidic structures contain one main chamber, one measuring chamber, and one reaction chamber. The injection chamber is used to load the sample. The weighing chamber is connected to the injection chamber and is used for sample pretreatment and sample weighing. The reaction chamber is connected to the metering chamber and samples that have been pretreated and metered from the metering chamber are collected. The sample can also be inspected directly on the microfluidic platform by inserting a measuring strip into the reaction chamber.

At least one of the embodiments of the present invention provides a method of operating the microfluidic test apparatus. In the first step, the sample and measurement strip are placed in the injection chamber and the reaction chamber of the microfluidic platform, respectively. The microfluidic platform then begins to rotate to allow the sample to flow from the main inlet chamber to the metering chamber. In the next step, the microfluidic platform vibrates to transfer the sample from the weighing chamber to the reaction chamber containing the measurement strip. The reaction starts when the sample and the measuring strip come into contact in the reaction chamber. When the reaction is completed, the reaction results are checked by a device or a manual method.

At least one characteristic of the embodiments of the present invention is that the sample pre-processing effect is excellent. The microfluidic inspection apparatus can rapidly separate the injected sample using a rotating unit (i.e., a rotating engine). By using the principle of centrifugal force and density difference, high-density material and low-density material are separated in a short time. This rapid sample separation can purify the sample in place and greatly improve the accuracy of the analysis results.

At least one feature of the embodiments of the present invention is that it exhibits excellent analytical stability and reproducibility. After the sample pretreatment is completed, the microfluidic inspection apparatus transfers low-density substances in the sample from the metering chamber to the reaction chamber in such a manner that the sample is vibrated using the vibration unit (i.e., the vibration engine) or alternately rotated in the counterclockwise direction. Using such a mechanical approach will significantly reduce artificial mistakes and variables. For example, in a microfluidic platform, transferring samples from a vibrating unit to a reaction chamber provides a consistent reaction condition and also improves analytical stability and reproducibility.

At least one feature of the embodiments of the present invention is the ability to control the sample injected from the metering chamber to the reaction chamber. The amount of transferred sample is determined by several variables, including the shape of the weighing chamber, the volume of the weighing chamber, the distance between the weighing chamber and the center of rotation, and the volume of the injected sample. In addition, the oscillation condition of the vibration unit can be changed to adjust the sample transfer capacity.

In the embodiment of the present invention, the microfluidic examination apparatus can perform analysis using a small amount of sample. The microfluidic device can be easily manufactured, the price is low, and consistent and reliable analysis results can be obtained in a short time. The microfluidic device can be applied to various fields such as chemical test, biochemical test, medical test, water quality test, environmental test, food inspection, and defense industry.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A is a diagram showing a microfluidic examination apparatus according to some embodiments of the present invention. FIG.
FIG. 1B is a view for explaining a connection relationship among constituent parts of a microfluidic examination apparatus according to some embodiments of the present invention. FIG.
2A illustrates a microfluidic platform with a discrete microfluidic structure in accordance with some embodiments of the present invention.
Figure 2B is a microfluidic platform with an integrated microfluidic structure in accordance with some embodiments of the present invention.
3A is a diagram illustrating a microfluidic structure in accordance with some embodiments of the present invention.
FIG. 3B is a view for explaining a connection relationship among components of a microfluidic structure according to some embodiments of the present invention. FIG.
4A is a diagram illustrating a microfluidic structure in accordance with some embodiments of the present invention.
FIG. 4B is a view for explaining a connection relationship among components of a microfluidic structure according to some embodiments of the present invention. FIG.
5 is a view for explaining a configuration of a microfluidic structure according to some embodiments of the present invention.
6 is a diagram illustrating a method of operating a microfluidic device according to some embodiments of the present invention.
FIG. 7A is a diagram showing a change in angular velocity of a rotating unit according to time according to some embodiments of the present invention. FIG.
FIG. 7B is a diagram showing a change in angular velocity of the vibration unit according to time according to some embodiments of the present invention. FIG.
8A-8D are diagrams illustrating steps of a method for operating a microfluidic test apparatus according to some embodiments of the present invention.
FIG. 9 is a diagram showing a stability test result according to some embodiments of the present invention. FIG.

At least one of the embodiments of the present invention is a microfluidic inspection apparatus comprising one drive module and one microfluidic platform. The drive module has one rotating unit and one vibrating unit, which are configured to drive and control the microfluidic platform. The microfluidic platform has one rotation center and at least one microfluidic structure and is configured for sample preprocessing and metering. The microfluidic platform is mounted on the drive module. Microfluidic structures further include a main inlet, metering chamber, and reaction chamber.

1A and 1B are views showing a microfluidic examination apparatus of some embodiments of the present invention. The microfluidic testing device was composed of one drive module (10) and one microfluidic platform (20). The microfluidic platform 20 may be mounted on the drive module 10 and used. This is because the drive module 10, which is composed of one rotary unit 11 and one vibration unit 12, is set up to drive and control the movement of the microfluidic platform 20. The microfluidic platform 20 has a center of rotation 21 and a circumference 22 and is used for sample preprocessing and metering. As shown in FIG. 1B, the microfluidic platform 20 further includes at least one microfluidic structure 50.

The driving module 10 shown in Fig. 1A may be a centrifuge consisting of one rotating unit 11 and one vibrating unit 12. The operating drive module 10 in operation may cause the microfluidic platform 20 to rotate, oscillate, or alternately rotate in clockwise and counterclockwise alternations.

The microfluidic platform 20 shown in FIG. 1A may be circular, quadrangular, polygonal, or any other radially symmetrical shape. The material of the microfluidic platform 20 may be selected from polyethylene, polyvinyl alcohol, polypropylene, flurostyrene, polycarbonate, fl uromethylmethacrylate, polydimethylsiloxane, silicon dioxide, or a combination of these materials.

As shown in FIGS. 1A and 1B, the microfluidic inspection apparatus may have one detection module 30. FIG. The detection module 30 is connected to the drive module 10 and is configured to acquire or sense a signal such as the inspection result of the microfluidic device. For example, the detection module 30 can be selected from a spectrophotometer, a colorimeter, a turbidimeter, a thermometer, a pH meter, an omega meter, a collimator, an image sensor, or a combination of the above instruments.

2A is a diagrammatic representation of a microfluidic platform with discrete microfluidic structures of some embodiments of the present invention. The microfluidic platform 20 is composed of a plurality of separated microfluidic structures 50 and each microfluidic structure 50 has one sample inlet chamber 40 and one sample inlet 41. Thus, the microfluidic structures 50 of the microfluidic platform 20 can perform the same or different tests individually using different samples.

Figure 2B is a microfluidic platform with integrated microfluidic structures of some embodiments of the present invention. The microfluidic platform 20 has one sample inlet chamber 40 ', one sample inlet 41, a plurality of subchambers 42, and a plurality of microfluidic structures 50. The main entrance chamber 40 'is installed at the center of the microfluidic platform 20 and connected to the plurality of microfluidic structures 50 through a plurality of subchambers 42. When a sample is injected through the injection port 41, a single sample is evenly distributed to each microfluidic structure 50 through the secondary chamber 42. The microfluidic platform 20 can perform multiple tests simultaneously.

In some embodiments of the present invention, the microfluidic platform 20 with a plurality of microfluidic structures 50 may be constructed as desired by combining the features of Figures 2a and 2b. For example, eight microfluidic structures of a microfluidic platform may be designed such that two microfluidic structures share one sample chamber, if necessary, to form four pairs of microfluidic structures. After the sample is injected into the injection chamber, the sample can be evenly distributed to the two microfluidic structures through the sump connected between the injection chamber and the two microfluidic structures. A pair of microfluidic structures can perform two tests simultaneously on the same sample.

3A is a diagram illustrating a microfluidic structure in accordance with some embodiments of the present invention. The microfluidic structure 50 shown in FIG. 3A includes one main inlet chamber 40A, one valve 70A, one transition chamber 517, one metering chamber 511A, one reservoir 515A, one first chamber 513A, One collection chamber 516, and one reaction chamber 514A. This microfluidic structure 50 may be installed on a circular microfluidic platform similar to the microfluidic platform 20 shown in FIG. In this case, the rotation center 21 of the microfluidic platform 20 is defined inside the microfluidic platform 20 and the periphery 22 is defined outside. The microfluidic structure 50 is composed of a main entrance chamber 40A, a valve 70A, a transition chamber 517, a measurement chamber 511A, and a storage chamber 515A in this order from the inside to the outside. The first chamber 513A and the collecting chamber 516 are located on the left and right sides of the measuring chamber 511A respectively and the reaction chamber 514A is installed outside the collecting chamber 516. [ The microfluidic structure 50 may be provided with several air holes 60 to reduce the resistance due to the air pressure generated when the sample moves within the microfluidic structure 50. In some situations, the sample may encounter resistance when flowing into the sealed chamber. The air holes reduce the air pressure at the local site and reduce the resistance to allow the sample to enter any room. For example, the air holes 60 can be installed in the gum chamber 517, the first-stream chamber 513A, or the collecting chamber 516 in Fig. 3A, and the storage chamber 515A, the reaction chamber 514A, Or in other portions of the microfluidic structure 50.

A sample can be placed in the sample inlet chamber 40A shown in Fig. 3A. For example, a blood sample, a urine sample, a needle sample, a water sample, or a liquid food sample can be put in. The sample may also consist of a high density material and a low density material. For example, it can be composed of blood cells and serum in a blood sample, a Jordanian bag and a jugular fluid in a sample of a body fluid, or a soil and water in a water quality sample obtained from a river.

The valve 70A shown in Fig. 3A is a capillary valve. However, it may be a mechanical valve and other well-known valves. The valve 70A is installed to prevent the sample from flowing into the buffer chamber 517 before the predetermined condition is met. For example, a capillary valve can limit the sample by greatly increasing the surface tension of the sample passing through the valve. When the centrifugal force applied by the rotating unit 11 (as shown in Fig. 1B) of the microfluidic testing apparatus reaches the limit and the centrifugal force is higher than the surface tension and the capillary force, the sample breaks through the capillary valve, (517).

The buffer chamber 517 shown in FIG. 3A is provided to delay the rate at which the sample flows into the measurement chamber 511A. If the rate at which the sample flows into the metering chamber 511A is faster than the air release rate of the microfluidic structure 50, the sample may leak to other parts of the microfluidic structure 50 because the air pressure in the metering chamber 511A is too large . This may result in degradation of sample preprocessing efficiency and analysis accuracy.

The collection chamber 516 shown in FIG. 3A was composed of one inlet and one outlet. The inlet of the collecting chamber 516 was connected to the measuring chamber 511A, and the outlet was connected to the reaction chamber 514A. Since the area of the inlet of the collecting chamber 516 is larger than the area of the outlet, the collecting chamber 516 is shaped like a funnel. In operation of the microfluidic device, the collection chamber 516 assists in collecting the sample flowed from the measurement chamber 511A by the reaction chamber 514A.

The reaction chamber 514A shown in FIG. 3A can be used to insert a measurement strip (as shown in FIG. 8) to inspect the sample in place. The measurement strip 80 may be litmus test strips, chlorine peroxide measurement strips, water quality hardness strips, blood glucose measurement strips, ovulation measurement strips, colloidal cold strips, Multistix® measurement strips or other measurement strips depending on the test item.

The first-flow chamber 513A shown in Fig. 3A can be used to receive a sample swept in the measuring chamber 511A. For example, when the measuring chamber 511A has the first set capacity and a large amount of the sample enters the measuring chamber 511A, the sample exceeding the set capacity flows into the first chamber 513A from the measuring chamber 511A . Therefore, the first-flow chamber 513A holds the sample in the measurement chamber 511A at the first set capacity by accepting the exceeded sample amount.

The first-stream chamber 513A shown in FIG. 3A has two small secondary chambers, and the central portion is connected to the capillary so that it looks like an hourglass. The shrunken middle portion of the hourglass structure prevents the sample from flowing back into the metering chamber 511A. The hourglass structure thus enhances the sample metering accuracy of the microfluidic structure 50.

The storage chamber 515A shown in Fig. 3A is used to accommodate the high density material separated from the sample after the centrifugal force operation of the rotation unit 11 (as shown in Fig. 1B). If the microfluidic structure 50 is designed to have several chambers, materials having different densities can be separately stored in the metering chamber 511A, the first-class chamber 513A, the storage chamber 515A, and other chambers. Therefore, the sample preprocessing efficiency of the microfluidic structure 50 can be improved. For example, after centrifugation, the high-density material of the sample is separated and stored in the storage chamber 515A, and the low-density material remains in the measurement chamber 511A. In some embodiments, the reservoir 515A is connected to the metering chamber 511A via a capillary. When the vibration unit 12 is operated, the capillary prevents the high-density material from flowing back to the measurement chamber 511A. The capillary tube maintains the sample volume and purity in the metering chamber 511A constant, thereby enhancing the analytical accuracy performed in the microfluidic structure 50.

Figure 3a shows the microfluidic structure 50 in some embodiments of the present invention. In other embodiments, the components of the microfluidic structure 50 may be increased or decreased in size and / or structure and / or shape by taking into account the need for inspection or cost.

FIG. 3B is a view showing a microfluid structure in some embodiments of the present invention, and shows a connection state between the components shown in FIG. 3A. FIG. The microfluidic structure 50 of FIG. 3B includes a sample inlet chamber 40A, a valve 70A, a buffer chamber 517, a metering chamber 511A, a storage chamber (not shown) 515A, a first-stream chamber 513A, a collecting chamber 516, and a reaction chamber 514A. Both ends of the valve 70A are connected to the sample main inlet chamber 40A and the buffer chamber 517 respectively and the buffer chamber 517 is connected to the measurement chamber 511A. Both ends of the collecting chamber 516 are connected to the measuring chamber 511A and the reaction chamber 514A, respectively. The connection portion between the collection chamber 516 and the reaction chamber 514A is referred to as a first connection passage 520A. The metering chamber 511A is connected to the first-class chamber 513A through the microfluidic channel 512A. The connection portion between the first-stream chamber 513A and the microfluidic channel 512A is referred to as a second connection passage 521A. The microfluidic channel 512A further has an outlet and is connected to the storage chamber 515A.

In some embodiments, the microfluidic channel 512A shown in Figure 3B further includes a turn portion 512 IA. This turn portion 5121A is C-shaped and the open portion faces the rotation center 21 (as shown in Fig. 1A) of the microfluidic platform 20. When the oscillation unit 12 is operated, the turn portion 5121A prevents the sample from flowing backward from the first-stream chamber 513A to the measurement chamber 511A. The turn portion 5121A enhances the analysis accuracy performed in the microfluidic structure 50 by making the sample volume and purity in the measurement chamber 511A constant.

4A is a diagram illustrating a microfluidic structure of some embodiments of the present invention. The microfluidic structure 50 shown in FIG. 4A includes a sample inlet chamber 40B, a measurement chamber 511B, a reservoir 515B, a first-flow chamber 513B, a solution inlet chamber 518, a reaction chamber 514B, a valve 70B), and a waste water chamber (519). This microfluidic structure 50 can be installed in a circular microfluidic platform similar to the microfluidic platform 20 shown in FIG. In this case, the rotation center 21 of the microfluidic platform 20 is the inside of the microfluidic platform 20 and the circumference 22 is the outside of the microfluidic platform 20. The microfluidic structure 50 was formed from the inside to the outside in the order of the sample inlet chamber 40B, the measuring chamber 511B, and the storage chamber 515B. The first-stream chamber 513B and the reaction chamber 514B are located on the left and right sides of the measurement chamber 511B, respectively. The solution inlet chamber 518 is installed inside the reaction chamber 514B and the wastewater chamber 519 is installed outside or nearby. The valve 70B connects the reaction chamber 514B and the waste water chamber 519.

The solution inlet chamber 518 shown in FIG. 4A receives the solution. The solution may enter the reaction chamber 514B directly without passing through the various components of the microfluidic structure 50. The solution injected into the solution inlet chamber 518 may be a buffer solution, a washing solution, a sample, or a solvent. For example, the sample strip 80 for sample analysis (as shown in FIG. 8A) is preserved in an inactive form, and upon sample analysis, the active agent flows into the reaction chamber 514B into the solution inlet chamber 518, 80). In another example, after the reaction of the sample with the measuring strip 80 is completed, the washing solution flows into the reaction chamber 514B through the solution inlet chamber 518 to wash the measuring strip 80. In another example, the measurement strip 80 used in the sample analysis is a chromatographic measurement strip, in which the buffer solution is injected into the solution inlet chamber 518 during sample analysis so that the rotation unit 11 (as shown in FIG. 1B) And flows into the reaction chamber 514B by centrifugal force generated when the chromatographic measurement strip is subjected to chromatographic analysis.

The waste water chamber 519 shown in Fig. 4A receives the solution discharged from the reaction chamber 514B. For example, if the sample remains in the reaction chamber 514B for too long, the sample may undergo excessive reaction of the measuring strip 80 (as shown in FIG. 8A), resulting in false positive results. In some other instances, the characteristics such as the color of the sample can interfere with the detection efficiency of the detection module 30 (as shown in FIG. 1B) when the sample remains in the reaction chamber 514B for too long, making analysis difficult. Therefore, by installing the waste water chamber 519, the sample or other solution discharged from the reaction chamber 514B can be accommodated.

The valve 70B shown in Fig. 4A is used as a capillary valve to control the flow rate of the solution. In some embodiments, however, the valves may be mechanical valves and other well known valves. In some situations, if the sample is discharged from the reaction chamber 514B to the waste water chamber 519 quickly without encountering any resistance, the reaction of the measurement strip 80 may be incomplete or the reaction may not be uniform. Thus, the provision of the valve 70B can prevent the sample from escaping too quickly from the reaction chamber 514B before the measurement strip 80 is fully reacted.

4A shows the microfluidic structure 50 in some embodiments of the present invention. In an alternative embodiment, the components of the microfluidic structure 50 may be increased or decreased in size, structure and shape may be adjusted to account for inspection needs and cost considerations.

FIG. 4B is a view showing a microfluid structure in some embodiments of the present invention, and shows a connection state between the components shown in FIG. 4A. FIG. The microfluidic structure 50 of FIG. 4B includes a sample inlet chamber 40B, a metering chamber 511B, a reservoir 515B, a first-flow chamber 513B, There are an inlet chamber 518, a reaction chamber 514A, a valve 70B, and a waste water chamber 519. The sample inlet chamber 40B is installed inside the measuring chamber 511B and connected to the measuring chamber 511B. The left and right sides of the measuring chamber 511B are connected to the first-stream chamber 513B and the reaction chamber 514B, respectively. The connecting portion between the measuring chamber 511B and the reaction chamber 514B is referred to as a first connecting passage 520B. A solution inlet chamber 518 shown in FIG. 4B is located inside the reaction chamber 514B and connected to the reaction chamber 518B. The waste water chamber 519 is installed outside or near the reaction chamber 514B and the valve 70B connects the reaction chamber 514B and the waste water chamber 519. [ The metering chamber 511B is connected to the first-class chamber 513B through the microfluidic channel 512B. The connection portion between the microfluidic channel 512B and the first-flow chamber 513B is referred to as a second connection passage 521B. In Fig. 4B, the microfluidic channel 512B has a turn portion 5121B. In some embodiments, a passageway protrudes into the spin portion 5121B and is connected to the storage chamber 515B.

Figure 5 illustrates the microfluidic structure in some embodiments of the present invention and illustrates the installation of components. The microfluidic structure 50 shown in FIG. 5 is composed of a sample inlet chamber 40C, a measurement chamber 511C, a storage chamber 515C, a first-flow chamber 513C, a solution inlet chamber 518, and a reaction chamber 514C . The connection portion between the measurement chamber 511C and the reaction chamber 514C is referred to as a first connection passage 520C and the connection portion between the first-stream chamber 513C and the microfluidic channel 512C is referred to as a second connection passage 521C.

The microfluidic structure 50 shown in Figure 5 may be installed between the rotation center 21 and the circumference 22 of a circular microfluidic platform similar to the microfluidic platform 20 shown in Figure 2a. In order to highlight the technical features of some embodiments, the perimeter 22, which should be a curve, is shown in a straight line. The first distance H1 is the distance between the circumference 22 and the first connection passage 520C and the second distance H2 is the distance between the circumference 22 and the second connection passage 521C. The first distance H1 is longer than or equal to the second distance H2. When the microfluidic structure 50 is installed in the circular microfluidic platform 20, the distance from the rotation center 21 to the first connection passage 520C is longer than the distance from the rotation center 21 to the second connection passage 521C Short or equal. For example, when the rotating unit 11 (as shown in FIG. 1B) is operated due to the difference in centrifugal position energy between the first connecting passage 520C and the second connecting passage 521C, an excess amount of sample is supplied to the measuring chamber 511C Flows into the first-stream chamber 513C instead of the reaction chamber 514C preferentially. The sample metering of the microfluidic structure 50 is therefore accurate. In another embodiment, the length of the first distance H1 and the second distance H2 may be designed differently to control the capacity of the metering chamber 511C.

FIG. 6 is a diagram showing an operation flow of a microfluidic examination apparatus according to some embodiments of the present invention. FIG. In the sample analysis, first the measurement strip is placed in the reaction chamber of the microfluidic platform, and the sample is injected into the injection chamber in the same microfluidic platform. The microfluidic platform then rotates to transport the sample from the main inlet chamber to the metering chamber. The microfluidic platform is then vibrated to transfer the sample from the metering chamber to the reaction chamber. After the reaction between the sample in the reaction chamber and the measurement strip is completed, the reaction results are detected and analyzed by an automatic method using a manual method or a detection module.

As an example of a microfluidic device having the microfluidic structure 50 of FIG. 3a coupled to the microfluidic device shown in FIG. 1b, the sample strip 80 (as shown in FIG. 8a) Into the reaction chamber (514A) of the fluid platform (20). The sample is then placed in the sample inlet chamber 40A of the microfluidic platform 20. The microfluidic platform 20 is then rotated to cause the sample in the sample inlet chamber 40A to be delivered to the metering chamber 511A. After the sample is transferred to the measurement chamber 511A, the microfluidic platform 20 is vibrated so that the sample of the measurement chamber 511A is transferred to the reaction chamber 514A. Finally, once the reaction of the sample in the reaction chamber 514A with the measurement strip 80 is completed, the reaction results of the measurement strip 80 are detected and analyzed in an automatic manner using a manual or detection module 30.

In some of the embodiments of Figure 6, the microfluidic platform used to operate the microfluidic testing device further includes a first chamber coupled to the storage chamber. After the sample has been transferred to the dosing chamber via centrifugation, some sample is first-streamed to the first-class chamber and the sample volume of the dosing chamber is reduced to the first set volume. The first set capacity used in the microfluidic structure 50 shown in Figure 5 was related to the capacity of the metering chamber 511C and also to the distance H2 from the perimeter 22 to the second connection passage 521C.

In some embodiments of FIG. 6, a vibration condition consisting of an appropriate vibration frequency and a vibration width is determined prior to vibrating the microfluidic platform, and shaking the sample through the vibration force causes the sample in the measurement chamber to flow into the connected reaction chamber. The capacity of the sample flowing into the reaction chamber is the second setting capacity. The magnitude of this second capacity is positively correlated with the oscillation frequency and vibrational amplitude at the time of vibrating the microfluidic platform and the amount of sample in the metering chamber 511C. However, the second setting capacity has a negative correlation with the viscosity of the sample.

7A is a diagram illustrating the angular velocity of a rotating unit over time in some embodiments of the present invention. The microfluidic platform 20 is driven when centrifugal force is generated by operating the rotation unit 11 of the drive module 10 shown in FIG. FIG. 7B is a view showing angular acceleration of a vibration unit according to time in some embodiments of the present invention. FIG. When the vibration unit 11 of the drive module 10 shown in FIG. 1B is operated, the drive module 10 vibrates the microfluidic platform 20 by switching between positive / negative angular velocities or between positive and negative angular accelerations .

8A-8D are diagrams illustrating steps of operating a microfluidic device in some embodiments of the present invention. 8A-8D is similar to the microfluidic testing apparatus shown in FIG. 1B with the microfluidic structure 50 of FIG. As shown in FIG. 8A, before starting the sample analysis in the microfluidic platform 20, the measurement strip 80 is placed in the reaction chamber 514C and the sample is injected into the main inlet chamber 40C. The injected sample consisted of a low density material 91 and a high density material 92. 8B, the angular velocity of the rotation unit 11 of the drive module 10 increases, and the low density material 91 and the high density material 92 of the sample flow into the measurement chamber 511C and the storage chamber 515C. An excess amount of the sample is first-streamed into the first-stream chamber 513C to maintain the sample volume of the measurement chamber 511C at the first set volume and prevent an excessive amount of the sample from flowing into the reaction chamber 514C. In FIG. 8C, the material in the sample is aligned with the microfluidic structure 50 based on the density gradient due to the centrifugal force of the rotating unit 11. Specifically, the high-density material 92 is located near the storage chamber 515C outside the microfluidic platform 20, and the low-density material 91 is located near the measurement chamber 511C inside the microfluidic platform 20, do. 8D, when the vibration unit 12 of the drive module 10 is operated, some of the sample in the measurement chamber 511C is transferred to the reaction chamber 514C to react with the measurement strip 80. [

Some embodiments of Figures 8a-8d have been related to a method of checking milk quality in the microfluidic platform 20 of Figure 2b. The microfluidic structure 20 is integrated in the microfluidic platform 20. The microfluidic platform 20 includes a sample inlet chamber 40 ', an inlet 41, eight subchambers 42, and eight microfluidic structures 50, Respectively. In the first step, the eight reaction chambers 514C of the microfluidic platform 20 are connected to a blood glucose measurement strip, a milk protein measurement strip, a pH measurement strip, a calcium measurement strip, a tetracycline measurement strip, a chloramphenicol measurement strip, Add the lactam measurement strip and inject 210 μL of milk into the sample inlet (40 '). The angular velocity of the microfluidic platform 20 is then raised to 600 RPM by the rotation unit 11 of the drive module 10 and the milk is divided and flows into the eight microfluidic structures 50. Since each dosing chamber 511C is designed to accommodate 25 mu L of milk, milk exceeding 25 mu L is dominated by a storage chamber 515C and a first-class chamber 513C. When the rotating unit continues to rotate at 600 RPM for 3 minutes, substances such as microorganisms and solidified substances in the milk are transferred to the storage chamber 515C due to the centrifugal force of the rotating unit 11. [ The lactation protein and the low sediment coefficient material remain in the measuring chamber 511C. The vibrating unit 12 of the driving module 10 is operated to transfer the milk of the measuring chamber 511C to the reaction chamber 514C with a vibration width of 720 degrees and a vibration frequency of 10 Hz, .

Some embodiments of FIGS. 8A-8D have been related to methods for inspecting the concentration of triglycerides in a blood sample in the microfluidic platform 20 shown in FIG. 2A. There are eight separate microfluidic structures 50 in the microfluidic platform 20. In the first step, 30 μL of blood samples from eight subjects are injected into the eight primary chamber 40C. Eight reaction chambers 514C contain a triglyceride strip. The actual sample volume for each primary chamber is 32 μL at 28 μL. This is because the manual injection is very unstable and there is a difference of about 5% in capacity. The rotation unit 11 of the drive module 10 increases the angular velocity of the microfluidic platform 20 to 5000 RPM and the blood sample flows into the microfluidic structure 50. At this stage, since each measuring chamber 511C is designed to accommodate a 25 mu L blood sample, each measuring chamber 511C contains a blood sample of the same volume. Blood samples in excess of 25-μL lead to storage chamber 515C and first-class chamber 513C. When the rotation unit 11 of the drive module 10 rotates at 5000 RPM for 90 seconds, the blood substances such as blood cells and coagulation are moved to the storage room 515C due to the centrifugal force of the rotation unit 11, 511C. The vibrating unit 12 of the driving module 10 is operated to transfer 10 μL of plasma of the measuring chamber 511C to the reaction chamber 514C with a vibration width of 720 degrees and a vibration frequency of 15 Hz, Lt; / RTI >

Some embodiments of Figures 8a-8d have been related to methods for inspecting pathogens in a blood sample in the microfluidic platform 20 shown in Figure 2b. The microfluidic platform 20 has an integrated microfluidic structure and the microfluidic platform 20 includes a sample inlet chamber 40 ', an inlet 41, eight subchambers 42, and eight microfluidic structures 50 ). In the first step, the eight reaction chambers 514C of the microfluidic platform 20 are each loaded with a hepatitis B surface antigen measurement strip, a hepatitis C antibody test cassette, a syphilis test cassette, a human immunodeficiency virus test cassette, a salmonella antigen measurement strip , A malaria antigen test cassette, a mycoplasma IgG measurement strip, and a Helicobacter IgG measurement strip, and injecting 68 μL of the blood sample into the main inlet (40 '). The rotating speed of the microfluidic platform 20 is then increased to 600 RPM with the rotating unit 11 of the drive module 10 and the blood sample is evenly distributed to the eight sub-chambers 42. When the rotating speed of the rotating unit 11 is increased to 5000 RPM, a valve (as shown in FIG. 2B) connecting the sub-chamber 42 and the measuring chamber 511C is ruptured and blood samples in the sub- ). Since each dosing chamber 511C is designed to accommodate 8 mu L of blood sample, a blood sample exceeding this capacity is dominated by the storage chamber 515C and first-class chamber 513C. When the rotating unit 11 of the driving module 10 rotates at 5000 RPM for 90 seconds, the blood high density material such as blood cells and coagulum moves to the storage room 515C due to the centrifugal force of the rotation unit 11, The substance remains in the measuring chamber 511C. The vibration unit 12 of the drive module 10 rotates alternately left and right for 15 seconds at a vibration frequency of 1080 degrees and a vibration frequency of 5 Hz to transfer 3.5 Pl of plasma of the measurement chamber 511C to the reaction chamber 514C To react with the measurement strip 80.

In some alternative embodiments, the eight microfluidic structures 50 of the microfluidic platform 20 may be designed with different structures. For example, syphilis test cassettes and human immunodeficiency virus test cassettes are recommended for use in whole blood sample testing, but the Helicobacter IgG measurement strips and mycoplasma IgG measurement strips are recommended for plasma sample testing. To carry out this analysis simultaneously, a customized microfluidic platform 20 consisting of several microfluidic structures 50 with a reservoir 515C or consisting of several microfluidic structures 50 without a reservoir 515C can be used .

Some embodiments of Figures 8a-8d have been related to a method of inspecting the drug sample fluid in the microfluidic platform 20 shown in Figure 2a. The microfluidic platform 20 has eight microfluidic structures 50. Three droplets of the subject fluid are contained in each main inlet chamber 40C of the microfluidic platform 20. Each of the eight reaction chambers 514C is provided with a single cold calorimetric strip such as a morphine measurement strip, a heroin measurement strip, an MDMA measurement strip, a cocaine measurement strip, an amphetamine measurement strip, a methamphetamine measurement strip, a THC measurement strip, Insert a measuring strip of valium. Since the dropper used in sample injection is very low in capacity stability, the sample volume in each primary chamber is 20 μL at 15 μL. The angular velocity of the microfluidic platform 20 is accelerated to 5000 RPM by the rotation unit 11 of the drive module 10 and the sample fluid flows into the microfluidic structure 50. Each of the measuring chambers 511C of this stage contains samples of the same volume of the sample. This is because the measuring chamber 511C is designed to accommodate 13 μL of the sample fluid. The wastewater exceeding this capacity is automatically led to the storage chamber 515C and the first-class chamber 513C. When the rotation unit 11 is operated for 12 seconds at 12000 RPM, a substance such as a yam bag moves to the storage chamber 515C due to the centrifugal force of the rotation unit 11, and the supernatant is kept in the measurement chamber 511C. The vibration unit 12 of the drive module 10 operates for 10 seconds at a vibration frequency of 180 degrees and a vibration frequency of 30 Hz to transfer 5.5 占 퐇 of the supernatant of the measurement chamber 511C to the reaction chamber 514C, (80).

In some embodiments, the method further includes injecting a solution into the reaction chamber 514C. For example, the response of some measurement strips may be incomplete because the properties of the sample fluid are different. In this case, the measuring strip 80 of the reaction chamber 514C may be washed by injecting 15 mu L of the washing solution into the solution inlet chamber 518. [

FIG. 9 is a diagram showing a stability test result according to some embodiments of the present invention. The stability check checks the efficacy of the first-class yarn when the sample volume is transferred from the weighing chamber to the reaction chamber. The structure of the two microfluidic structures used in the stability test is similar to the microfluidic structure 50 shown in Fig. The difference is one microfluidic structure 50 (A) with first-class room 513A and the other is microfluidic structure 50 (B) without first-class room 513A. According to the data of FIG. 9, the microfluidic structure 50 (A) with the first-class chamber 513A has an injection error of about 3%, and the microfluidic structure 50 (B) And an injection error of about 25%. Therefore, the stability of the microfluidic structure 50 with the first-class chamber 513A is better than the microfluidic structure 50 without the first-class chamber 513A. When using the microfluidic structure 50 without the first-class chamber 513A, it is possible to add a design for enhancing the metering effect or to improve the metrological stability using the precise capacity measurement in advance.

The embodiments of the present invention are only examples, and the present invention is not limited thereto. Anything that has substantially the same constitution as the technical idea described in the claims of the present invention and achieves the same operational effects is included in the technical scope of the present invention. Accordingly, those skilled in the art will recognize that various changes, substitutions, alterations, and alterations can be made hereto without departing from the spirit of the invention as defined in the appended claims. I will say.

10: drive module 11: rotation unit
12: vibrating unit 20: microfluidic platform
21: center of rotation 22: perimeter
30: Detection module
40, 40 ', 40A, 40B, 40C: sample main entrance room
41: Sample inlet 42:
50: Microfluidic structures 511A, 511B, 511C: Measuring chamber
512A, 512B, 512C: Microfluidic channel
5121A, 5121B: Microfluidic channel turning portion
513A, 513B, 513C: first-stream chambers 514A, 514B, 514C:
515A, 515B, 515C: storage room 516: collection room
517: Waist chamber 518: Solution main chamber
519: waste water chamber 520A, 520B, 520C: first connection passage
521A, 521B, 521C: second connection passage
60: air hole 70A, 70B: valve
80: Measurement strip 91: Low density material
92: High density material H1: First distance
H2: Second street

Claims

In a microfluidic examination apparatus,
A drive module including a rotating unit and a vibration unit,
And a microfluidic platform mounted on the drive module and controlled by the rotation unit and the vibration unit,
Wherein the microfluidic platform comprises one rotation center and at least one microfluidic structure,
Each of the microfluidic structures includes a first,
One main entrance to the sample;
One measuring chamber connected to the injection chamber; And
And one reaction chamber connected to the measurement chamber and for inserting the measurement strip.

The method according to claim 1,
Wherein the microfluidic platform has a plurality of microfluidic structures wherein at least two inlet chambers are connected and integrated with each microfluidic structure.

The method according to claim 1,
Wherein the microfluidic structure comprises:
One first class room; And
And a microfluidic channel connected between the metering chamber and the first-stream chamber.

The method of claim 3,
Wherein the metering chamber and the reaction chamber are connected in a first connection passage, the microfluidic channel and the first-flow chamber are connected in a second connection passage, the distance from the rotation center to the first connection passage is a distance from the rotation center to the second connection passage Or a little shorter than that of the microfluidic device.

The method of claim 3,
Wherein the microfluidic structure further comprises a storage chamber connected to the microfluidic channel.

The method according to claim 1,
Wherein the microfluidic structure further comprises one collection chamber provided between the metering chamber and the reaction chamber,
The collecting chamber
One inlet connected to the metering chamber and one outlet connected to the reaction chamber,
Wherein the area of the inlet is greater than the area of the outlet.

The method according to claim 1,
Wherein the microfluidic structure further comprises a waste water chamber connected to the reaction chamber.

A method for operating a microfluidic device according to claim 1,
Inserting a measurement strip into a reaction chamber of the microfluidic platform of the microfluidic device;
Injecting a sample into the injection chamber of the microfluidic platform;
Rotating the microfluidic platform to transfer the sample from the main inlet chamber to the metering chamber;
Vibrating the microfluidic platform to transfer the sample from the metering chamber to the reaction chamber; And
And obtaining and analyzing the result of the inspection.

9. The method of claim 8,
The microfluidic platform further includes a first-class chamber,
Wherein rotating the microfluidic platform comprises:
Centrifuging the sample to transfer the sample from the main inlet chamber to the metering chamber;
Forcing the sample to flow in the metering chamber to the first-class room; And
Measuring the sample volume so that the sample volume of the metrology chamber is reduced to a first predetermined volume.

9. The method of claim 8,
Wherein vibrating the microfluidic platform comprises:
Determining a vibration frequency and a vibration width;
Wave vibrating the sample such that the sample in the measuring chamber is shaken; And
And transferring the sample so that a second predetermined sample volume is transferred to the reaction chamber.